Department of Environmental Health, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, Liaoning, People's Republic of China.
Department of Environmental Health, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, Liaoning, People's Republic of China.
Toxicol Lett. 2022 Apr 15;359:55-64. doi: 10.1016/j.toxlet.2022.01.020. Epub 2022 Feb 2.
Methylmercury (MeHg) is a bio-accumulative global environmental contaminant present in fish and seafood. MeHg accumulates in the aquatic environment and eventually reaches the human system via the food chain by bio-magnification. The central nervous system is the primary target of toxicity and is particularly vulnerable during development. It is well documented that developmental MeHg exposure can lead to neurological alterations, including cognitive and motor dysfunction. Apoptosis is a primary characteristic of MeHg-induced neurotoxicity, and may be regulated by autophagic activity. However, mechanisms mediating the interaction between apoptosis and autophagy remains to be explored. Autophagy is an adaptive response under stressful conditions, and the basal level of autophagy ensures the physiological turnover of old and damaged organelles. Autophagy can regulate cell fate through different crosstalk signaling pathways. A complex interplay between autophagy and apoptosis determines the degree of apoptosis and the progression of MeHg-induced neurotoxicity as demonstrated by pre-clinical models and clinical trials. This review summarizes recent advances in the roles of autophagy and apoptosis in MeHg neurotoxicity and thoroughly explores the relationship between them. The autophagic pathway may be a potential therapeutic target in MeHg neurotoxicity through modulation of apoptosis.
甲基汞（MeHg）是一种在鱼类和海鲜中存在的生物累积性全球环境污染物。MeHg 在水生环境中积累，最终通过食物链在生物放大作用下到达人体系统。中枢神经系统是毒性的主要靶标，在发育过程中尤其脆弱。有大量文献记载表明，发育过程中接触 MeHg 会导致神经功能改变，包括认知和运动功能障碍。细胞凋亡是 MeHg 诱导的神经毒性的主要特征，并且可能受到自噬活性的调节。然而，介导细胞凋亡和自噬之间相互作用的机制仍有待探索。自噬是应激条件下的一种适应性反应，自噬的基础水平可确保旧的和受损细胞器的生理周转。自噬可以通过不同的交叉信号通路调节细胞命运。自噬和细胞凋亡之间的复杂相互作用决定了细胞凋亡的程度和 MeHg 诱导的神经毒性的进展，这已在临床前模型和临床试验中得到证实。本综述总结了自噬和细胞凋亡在 MeHg 神经毒性中的作用的最新进展，并深入探讨了它们之间的关系。自噬途径可能通过调节细胞凋亡成为 MeHg 神经毒性的潜在治疗靶点。
